BME Seminar Series

Event Date: April 17, 2013
Time: 9:30 a.m.
Location: MJIS 1001, WL campus
"Rapid Evaporative Ionization Mass Spectrometry – mechanism, instrumentation and applications for biomarker analysis" presented by Zoltan Takats, Ph.D., Reader in Medical Mass Spectrometry, Department of Surgery and Cancer, Imperial College London.

The recently developed Rapid Evaporative Ionization Mass Spectrometry (REIMS) method is based on the thermal disintegration of liquid or solid phase samples containing already dissociated organic or inorganic ions. Solvated ions are transferred to gas phase via a mechanism showing similarities to that of thermospray (filament-off mode) or sonic spray ionization. Rapid heating is generally achieved by using electric current in case of electrically conductive samples or alternatively by laser ablation. Detailed investigation of the REIMS process has revealed an unusual, two-step ionization mechanism comprising the formation of large, electrically charged molecular clusters on the evaporation of the sample, which undergo a surface induced dissociation (SID) process in the first or second vacuum regime of the mass spectrometer. As a consequence, REIMS requires novel type of atmospheric interface setup designed to facilitate the dissociation of molecular clusters and to minimize memory effects caused by an EDI (electrospray droplet impact)-like phenomenon.

Although REIMS exhibits a fairly low ion yield, it still enables some very unique applications, most notably the in-vivo analysis of unicellular and multicellular organisms. Evaporation of biological tissues by means of Joule-heating is widely employed in surgery in form of electrosurgical coagulation or dissection. As a consequence, electrosurgical devices may serve as ion sources if coupled with appropriate mass spectrometric analyser. Rapid evaporation of biological tissues results in the formation of intact complex lipid molecular ions. The distribution of these species have already been demonstrated (by DESI and MALDI imaging MS studies) to elicit perfect histological specificity, hence the electrosurgical REIMS technique or so-called intelligent knife (iKnife) is capable of identifying dissected tissues in-vivo and real-time. Rapid tissue identification is based on the building of multivariate statistical models using histologically authentic spectra and localizing unknown data points in the model in the course of surgical interventions. This strategy allows identification times in the range of milliseconds, which – together with the ion transfer and mass analysis – allows tissue identification with 0.2-0.3 s delay relative to surgical procedure. The technique has recently been tested in human surgical environment for the in-vivo assessment of margins in case of solid tumour resection interventions. The study revealed close to 100% correct classification performance in case of the malignant tumours of the gastrointestinal tract, lungs, liver, kidneys, breast and brain as it was validated by histopathology. Recent results show that the specificity of REIMS data may go beyond differences in tissue morphology and mass spectral information can also be used to establish of the status of genetic/protein expression markers ranging from KRAS mutation to HER2 status.

REIMS technology – similarly to MALDI and DESI – has also been successfully used for the identification of intact bacterial cells. REIMS method does not require sample preparation, not even the harvesting of the cells, since analysis is directly performed on solid or in liquid culturing medium. Specificity of the method has been successfully demonstrated at genus, species and strain level, with correct classification values in the range of 97-100%. REIMS technique also enables the identification of pathogens in-situ, without sampling and culturing. H. pylori and C. difficile has been successfully identified by the analysis of gastric and colon mucosal samples. The parallel analysis of human tissues and associated microflora enables the development of a novel type of device termed ‘intelligent endoscope’ (iEndoscope) for the systems-level assessment of mucosa-associated microbiome in-situ. The device is envisioned to yield predictive information in case of chronic diseases associated with altered microflora ranging from inflammatory diseases through cancer to obesity and diabetes.

The seminar will be teleconferenced to SL-220 at IUPUI.

~BME Faculty Host: Dr. Zheng Ouyang~

***Coffee and juice will be provided at West Lafayette***